The purpose of this study is to examine whether two transdiagnostic dimensions - reduced reward anticipation (RRA) and heightened sensitivity to potential threat (SPT) - represent risk factors for internalizing (i.e., depression and anxiety) psychopathology. The proposed project is significant because internalizing psychopathologies are very heterogeneous, raising questions as to the validity of the categorical diagnostic nomenclature (e.g., DSM-IV). This study therefore takes the Research Domain Criteria (RDoC) approach and seeks to identify underlying dimensional constructs that cut across traditional categories of psychopathology. However, the proposed project extends the aims of RDoC by examining whether the proposed dimensional constructs reflect 1) risk markers for psychopathology (defining risk via the classic family study method) and 2) separable constructs (i.e., the discriminant validity of RDoC constructs). Specifically, we hypothesize that RRA (but not SPT) will predict risk for depressive symptomatology and SPT (but not RRA) will predict risk for certain anxiety symptoms (e.g., panic). We will recruit 210 probands with a wide range of internalizing psychopathology from the community and assess RRA and SPT using multiple physiological, behavioral, and self-report measures. Our primary indicators of RRA and SPT will be EEG alpha asymmetry while anticipating reward and startle response while anticipating a potential threat, respectively. These psychophysiological variables have been used extensively as measures of RRA and SPT and both tap anticipatory affective states, thus sharpening our test of discriminant validity. In addition, the startle task assesses sensitivity to acute threat a well as potential threat and therefore allows a test of the discriminant validity of RRA and SPT from this third RDoC construct (acute threat). The study aims to examine: 1) whether RRA and SPT predict family history (assessed via direct interview of 1st degree relatives) of separable facets of internalizing psychopathology; 2) whether indicators of RRA and SPT are abnormal in 'healthy' (or low symptom) age-matched siblings of probands with high levels of internalizing symptoms; 3) the familial aggregation of RRA and SPT; and 4) the construct validity of our electrophysiological measures of RRA and SPT using cardiovascular, behavioral, and self- report indicators of these two constructs. The impact of the study would be in identifying important underlying mechanisms that play a role in the etiopathogeneses of internalizing psychopathology. In addition, if these indicators prove to be familial markers of risk for psychopathology, they would make excellent (and relatively inexpensive) laboratory targets for prevention/early intervention efforts as well as targets for treatment development studies. PUBLIC HEALTH RELEVANCE: The proposed project takes a novel approach to identifying risk factors for internalizing psychopathology (i.e., depression and/or anxiety) by examining whether variation on particular underlying dimensions connote risk for these debilitating and costly conditions. Specifically, this study will examine whether a reduced sensitivity to reward and a heightened sensitivity to threat represent separable dimensions of risk for depression and certain types of anxiety symptoms.